The purpose of this application is to request funds to support the 3rd European Union (EU)/United States (US) Workshop on "Systems Level Understanding of DNA Damage Responses" to be held at Hotel Zuiderduin inEgmond aan Zee, Netherlands from March 30 to April 1, 2009. This third meeting in 2009 will refine the role of DNA damage response (DDR) networks in human disease and will further characterize responses to environmental exposures that are expressed through changes in DDR. Environmental exposures that produce DNA damage can include chemical carcinogens, represented as alkylating and oxidizing agents and heavy metals found in cigarette smoke, pesticides and industrial chemicals. In addition, physical damaging agents found in our natural environment, which include ionizing radiation associated with radon gas and UV radiation associated with sunburns are also major sources of exposure that can cause DNA damage and promote cancer. Each of the chemical and physical exposure types has the propensity to damage DNA and these agents will be discussed at the meeting in the context of the DDR. The goals of this 3rd joint EU/US workshop are twofold: (1) to assess the current science of the DDR, with specific attention on the influence of global and network level responses to environmental exposures that cause DNA damage, and the role of integrated DDR signaling pathways in the etiology of human diseases and;(2) to establish the basis for a reciprocal scientific exchange program between the EU and the US in the relevant areas of DDR research.